Hepatitis: Cheong JY

Cheong JY. · Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea. · Korean J Gastroenterol. · Pubmed #18604135 links to  free full text

Abstract: Chronic hepatitis B (CHB) is a serious health problem in Korea. The natural history of chronic HBV infection has been divided into 4 phases: immune tolerance, immune clearance, inactive HBsAg carrier state and reactivation. During the phases of immune tolerance and inactive HBsAg carrier state, no treatment is required. Patients in the immune clearance or reactivation phases are candidates for therapy. In the last years, treatment effects of CHB have considerably improved. Several agents are currently approved for the treatment of CHB: interferon alpha, pegylated interferon alpha, lamivudine, adefovir, entecavir, telbivudine and clevudine in Korea. The treatment recommendations from the 2004 Korean Association for the Study of the Liver guideline on the management of CHB have been updated to incorporate new therapeutic options. What is uncertain is which agent or combination of agents is most effective, how long therapy should last, and which criteria should be used to start, continue, switch or stop therapy. Issues for consideration include efficacy, safety and incidences of resistance, and method of administration of antiviral therapy in treatment-naive patients.

Kwon HC, Cheong JY, Cho SW, Choi JM, Hong SP, Kim SO, Yoo WD. · Department of Gastroenterology, Genomic Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, South Korea. · J Gastroenterol Hepatol. · Pubmed #19196395 No free full text.

Abstract: BACKGROUND: To evaluate the effect of reversion to YMDD wild-type on emergence of adefovir (ADV)-resistant mutation and antiviral activity of ADV in lamivudine (LAM)- resistant patients. METHODS: We determined YMDD mutations and ADV-resistant mutations before and every 3 months during ADV monotherapy in 33 LAM-resistant patients using the restriction fragment mass polymorphism (RFMP) method. RESULTS: Reversion to pure YMDD wild-type hepatitis B virus (HBV) occurred in 6% (2/33), 9% (3/33), 20% (4/20) and 35% (6/17) of patients after 12, 24, 36 and 48 weeks, respectively. Five (29%) patients were found to have pure YMDD mutants at 48 weeks of therapy. Among 33 patients, 4 (12%) patients developed ADV-resistant mutations at 48 weeks of therapy. Adefovir-resistant mutants emerged in all patients after reversion to YMDD wild-type HBV. The mean serum HBV reductions, evaluated at 24 weeks of therapy, were not different between patients with and without reversion to YMDD wild-type HBV (-3.1 log(10) copies/mL vs-3.4 log(10) copies/mL, P > 0.05). CONCLUSIONS: ADV-resistant mutations emerged after reversion to YMDD wild-type in LAM-resistant patients who received ADV monotherapy. Thus, ADV add-on therapy may be necessary to reduce the incidence of developing ADV resistance in patients with LAM resistance.

Cha CK, Kwon HC, Cheong JY, Cho SW, Hong SP, Kim SO, Yoo WD. · Internal Medicine, CHA Biomedical Center, Pochon CHA University College of Medicine, Seoul, South Korea. · J Med Virol. · Pubmed #19152409 No free full text.

Abstract: Adefovir has a potent antiviral activity as a rescue treatment against lamivudine-resistant strains. The aim of this study was to assess the patterns of lamivudine-resistant mutations and their influence on the virologic response to adefovir rescue therapy in patients with lamivudine-resistant chronic hepatitis B. Sixty-seven patients with lamivudine-resistant chronic hepatitis B were treated with adefovir monotherapy. Baseline blood samples were analyzed for lamivudine-resistant mutations via restriction fragment mass polymorphism. Virologic responses, ALT normalization and loss of HBeAg were assessed. Serum HBV DNA levels were measured using real-time PCR at baseline and 24 weeks of adefovir therapy. Of the 67 patients with chronic hepatitis B, 65 patients (97%) had lamivudine-resistant mutations in the YMDD motif [27 (41%) rtM204I, 22 (34%) rtM204V, and 16 (25%) rtM204I/V]. In addition to the YMDD mutations, the rtL180M, rtL80I, and rtV173L mutations were also present in 78%, 43%, and 11% of patients, respectively. The rtM204V mutation always accompanied rtL180M, and rtL80I was always observed in conjunction with rtM204I. Decrease in mean serum HBV did not differ between patients carrying the rtM204I versus rtM204V mutant at week 24 (-3.3 vs. -3.3 log(10) copies/ml, respectively; P = 0.303). The presence of the rtL180M, rtL80I, and rtV173L did not significantly affect viral load reduction during adefovir administration. These results demonstrate that the rtL80I mutant is co-selected with rtM204I as a compensatory mutation in the same manner as rtL180M with rtM204V, and that adefovir shows similar antiviral efficacy against all of the evaluated patterns of lamivudine-resistant HBV mutations.

Koh KH, Kang CJ, Kim DH, Choi YW, Kim MJ, Cheong JY, Cho SW. · Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea. · Korean J Gastroenterol. · Pubmed #19077481 links to  free full text

Abstract: Clevudine is a nucleoside analog of the unnatural beta-L configuration which has potent antiviral activity against hepatitis B virus (HBV). Clevudine is expected to have similar pattern of resistance profile as lamivudine. However, there was no report on the mutation associated with clevudine resistance in patients with chronic hepatitis B. We report a case of young male patient with chronic hepatitis B who presented with clevudine resistance. The patient had received lamivudine therapy for 5 months with reduced serum HBV DNA levels. Then, lamivudine was switched to clevudine monotherapy. After the 6 months of clevudine therapy, the patient developed virologic breakthrough (>1.0chi10(8) copies/mL) as well as biochemical breakthrough, which was associated with the presence of rtM204I plus rtL80I mutant. After switching from clevudine to adefovir, the viral load decreased with biochemical improvement.

Lee SK, Yi CH, Kim MH, Cheong JY, Cho SW, Yang SJ, Kwack K. · Medical Genomics Laboratory, Graduate School of Life Science and Biotechnology, Pochon CHA University, Seongnam, Korea. · Tissue Antigens. · Pubmed #19000145 No free full text.

Abstract: Collagen type III alpha 1 (COL3A1) is one of the extracelluar matrix (ECM) proteins. The expression of COL3A1 is closely related to chronic liver diseases. In this study, we investigated whether single nucleotide polymorphisms (SNPs) of COL3A1 confer genetic susceptibility to patients with hepatitis B virus-infected liver diseases including chronic hepatitis B (CH), liver cirrhosis (CIR), and hepatocellular carcinoma (HCC). A total of 399 Korean (KOR) people, 111 patients with CH, 95 patients with CIR, 86 patients with HCC, and 107 spontaneously recovery, were genotyped for 16 SNPs of the COL3A1 gene. The 'A' allele of rs3106796 was highly associated with the CH [odds ratio (OR) = 1.62, P = 0.01], CIR (OR = 1.67, P = 0.01), and HCC (OR = 1.59, P = 0.03). There were six polymorphic SNPs that could be divided into two linkage disequilibrium (LD) blocks. The haplotype pattern of the KOR control seems to be similar to the patterns displayed in the Japanese, Chinese, and Caucasian populations sampled in the International HapMap project. Haplotype 3 (A-G-A) of the LD block 2 was significantly associated with CH (OR = 2.23, P = 0.02), CIR (OR = 2.24, P = 0.03), and HCC (OR = 2.27, P = 0.03). Moreover, diplotype analysis showed that they had increased relative risk for CH and CIR in the two diplotypes, dt3 (A-G-A/G-G-A; OR = 4.05, P = 0.01) and dt6 (A-A-A/A-G-A; OR = 7.42, P = 0.01 and OR = 5.84, P = 0.05) against dt1 (G-G-A/G-G-A), the most common diplotype in both KOR groups. In vitro reporter gene assays showed that the constructs containing the 'G' allele of rs3106796 appear to exert lower transcriptional activity of COL3A1 than the 'A' allele, depending on the promoter types.

Cho SW, Cheong JY, Ju YS, Oh do H, Suh YJ, Lee KW. · Department of Gastroenterology, Genomic Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, Korea. · J Korean Med Sci. · Pubmed #18955791 links to  free full text

Abstract: It has been speculated that human leukocyte antigen (HLA) alleles are associated with the outcome of hepatitis B virus (HBV) infection although the data obtained from various populations have shown some inconsistencies. A total of 464 HBVinfected Korean individuals (80 spontaneously recovered [SR] and 384 chronically infected [CI]) were selected to investigate the association of HLA class II alleles with the viral clearance and persistence. Our results showed that: 1) multiple HLA class II alleles and haplotypes were associated with viral clearance (DRB1*1302, DRB1*1502, DQB1*0302, DQB1*0609, and related-haplotypes) and persistence (DRB1*0701, DQB1*0301, and related-haplotypes); 2) DRB1*1302 and DQB1* 0609 were more strongly associated with viral clearance. And the association of DQB1*0609 (pc=0.0084; OR, 7.24) with vial clearance was much stronger than previously recognized, DRB1*1302 (pc=0.0038; OR, 4.34); and 3) linkage to a specific DPB1 allele in a haplotype strengthened the association with viral clearance, although DPB1 itself was not associated with the outcome. These results indicate the existence of multiple factors controlling viral clearance in the HLA class II gene region. Further extended investigation on the genetic factors related to the outcome of HBV infection will provide valuable insights into the understanding of the mechanisms involved.

Cheong JY, Cho SW, Yoo JH, Hong SP, Kim SO, Yoo WD, Kim JH. · Department of Gastroenterology, Ajou University School of Medicine, Youngtong-ku, Suwon 442-721, South Korea. · Hepatogastroenterology. · Pubmed #18705323 No free full text.

Abstract: BACKGROUND/AIMS: Evolution of precore genes can occur during lamivudine therapy in HBV infection. This study investigated the changes in precore regions in patients treated with lamivudine and the pattern during relapse. METHODOLOGY: The sequences of codon 28 in precore region in serial samples of 16 patients with HBV (11 HBeAg-positive and 5 HBeAg-negative) treated with lamivudine were analyzed by restriction fragment mass polymorphism. RESULTS: Among 9 patients who had wild-type virus, the wild-type virus was replaced by A1896 during relapse after initial treatment in 2 patients, and a pure population with A1896 selected during relapse in all 4 patients with mixed infection. In 5 patients with A1896 during relapse, 3 patients initially reverted to wild-type and later selected A1896, and 2 patients maintained A1896 during lamivudine retreatment. In 8 patients showing HBeAg negative reactivation, 3 patients showed A1896 and 5 patients showed wildtype virus. CONCLUSIONS: Lamivudine therapy induced initial reversion from precore mutants to wild-type virus, but precore mutants reappeared in patients infected with precore mutants. In some patients infected by wildtype HBV, wild-type HBV was replaced by precore mutants, resulting in a flare-up of hepatitis after cessation of lamivudine administration, and HBeAg negativity did not always correspond to the presence of precore mutants.

Lee SK, Kim MH, Cheong JY, Cho SW, Yang SJ, Kwack K. · Medical Genomics Laboratory, Graduate School of Life Science and Biotechnology, Pochon CHA University, SeongNam, Korea. · Liver Int. · Pubmed #18694400 No free full text.

Abstract: BACKGROUND/AIMS: Integrins are cell surface receptors for extracellular matrix (ECM) proteins that initiate signalling pathways that modulate proliferation, survival, invasion or metastasis. Consequently, integrins are potential targets for the treatment of cancer. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in integrin alpha(V) (ITGAV) in a Korean population were associated with chronic hepatitis B virus (HBV) infection and HBV-infected hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Thirteen ITGAV SNPs in 111 cases of chronic HBV infection, 86 cases of HBV-infected HCC and 107 cases of acute self-limited HBV infection were genotyped using Illumina's Sentrix array matrix (SAM) chip. RESULTS: The ITGAV intron SNPs rs9333289 and rs11685758, the 3'-untranslated region SNP rs1839123 and haplotype 3 (T-T-A) were associated with enhanced susceptibility to HBV-infected HCC (OR=1.75-2.42; P=0.02-0.05), while the intron SNP rs2290083 was associated with both chronic infection and HBV-infected HCC (OR=1.73-2.01; P=0.01-0.04). In addition, both rs2290083 and ht1 (C-C-G) were associated with the age at which chronic infection occurred, as determined by Cox relative hazard analysis (RH=1.39-1.62, P=0.04-0.01) CONCLUSION: ITGAV SNPs and haplotypes may be genetic factors that increase the susceptibility of Koreans to chronic HBV infection and HBV-infected HCC.

Kim DJ, Kim HS, Yim HJ, Suh JI, Cheong JY, Kim IH, Tark WY, Lee YS, Lee S, Lee JY. · Department of Internal Medicine, Hallym University College of Medicine, Korea. · Korean J Hepatol. · Pubmed #18617759 links to  free full text

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Cho JH, Cheong JY, Kang JK, Park JS, Lee MH, Lim NK, Hong SP, Kim SO, Yoo WD, Cho SW. · Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea. · Korean J Hepatol. · Pubmed #18367858 links to  free full text

Abstract: BACKGROUND/AIMS: Adefovir dipivoxil (adefovir) effectively inhibits both wild-type and lamivudine-resistant hepatitis B virus (HBV) replication. The development of adefovir resistance is both delayed and infrequent compared with lamivudine resistance. The aim of this study was to characterize the serologic, biochemical, and virologic response to adefovir, and to explore the factors affecting initial virologic response (IVR, defined as a decrease in serum HBV below 4 log10copies/mL after 6 month of treatment) and adefovir resistance in lamivudine resistant HBV-infected patients. METHODS: This study population comprised 76 patients with lamivudine-resistance who had received adefovir for more than 12 months between March 2004 and December 2006. The adefovir-resistant mutant was assayed at 6 months and 12 months during adefovir administration. Restriction-fragment mass polymorphism analysis was used for detecting YMDD and adefovir mutants. RESULTS: After adefovir administration, an IVR was observed in 31% of the patients with lamivudine resistance. Factors associated with an IVR were HBeAg negativity (P=0.04) and the presence of liver cirrhosis (P=0.04). Age, sex, pretreatment levels of alanine aminotransferase and aspartate aminotransferase, pretreatment HBV DNA levels, presence of precore mutation, and type of YMDD mutants were not related to an IVR during adefovir treatment. The prevalence of adefovir resistance was 5% and 13% at 6 months and 12 months after therapy, respectively. Mixed infection of the precore mutant was a risk factors for the emergence of adefovir resistance (P=0.01). CONCLUSIONS: Lamivudine-resistant HBV patients exhibiting HBeAg negativity and liver cirrhosis were more likely to achieve an IVR after adefovir therapy. Adefovir resistance was associated with mixed infection of the precore mutant.

Cheong JY, Cho SW, Lee JA, Lee KJ, Wang HJ, Lee JE, Kim JH. · Department of Gastroenterology, Genomic Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, Korea. · J Korean Med Sci. · Pubmed #18303200 links to  free full text

Abstract: The reasons for the viral persistence of hepatitis B virus (HBV) infection are unknown, but are probably related to host immune factors. Several matrix metalloproteinases (MMPs) can regulate an inflammatory response. The aim of this study was to assess the effects of the single nucleotide polymorphisms (SNPs) of MMP-3 and -9 genes on the susceptibility to persistent HBV infection. We studied 489 Korean patients with HBV infection (144 inactive carriers, 182 chronic hepatitis, and 163 liver cirrhosis) and 174 healthy individuals who had recovered from HBV infection. MMP-3 gene SNPs were identified at two polymorphic sites (codon 45 [E45K] and codon 96 [D96D]) and MMP-9 gene SNPs at three polymorphic sites (codon 279 [R279Q], codon 607 [G607G], and codon 668 [Q668R]) in study subjects. The frequency of T allele at third position of codon 96 in the MMP-3 gene was higher in HBV persistence patients when analyzed by co-dominant model (age- and sex-adjusted OR=1.242, 95% CI= 1.001-1.540, p=0.049). In conclusion the T allele at the third position of codon 96 in the MMP-3 gene might be associated with persistent HBV infection.

Park JS, Cheong JY, Kang JK, Cho JH, Yu S, Shin HD, Park BL, Cho SW. · Department of Gastroenterology, Genomic Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, Korea. · Korean J Gastroenterol. · Pubmed #18159163 links to  free full text

Abstract: BACKGROUND/AIMS: Infection with hepatitis B virus (HBV) may result in various conditions. Natural course of HBV infection is influenced by various host immune factors and cytokines play a crucial role in host immune defense. This study was undertaken to investigate the association between HBV persistence and development of hepatocelluar carcinoma (HCC) and single nucleotide polymorphisms (SNPs) of interleukin (IL)-12A. METHODS: Between March 2002 and December 2004, seven hundred thirty Korean patients with HBV infection and 320 healthy individuals who recovered from HBV infection were enrolled. We assessed polymorphisms and haplotype in IL-12A, and the genotype distributions of the HBV clearance and persistence groups were compared in order to investigate the association between HBV persistence and SNPs of IL-12A. Moreover, the genotypic distributions between patients with HCC and without HCC were compared to investigate the association between the development of HCC and SNPs of IL-12A. RESULTS: We asssesed the SNPs of IL-12A at position +6400, +6624 and +7003. On the basis of logistic regression analysis, no statistically significant association with HBV persistence was observed with IL-12A exon 7 +6400, +6624, 3' UTR +7003 SNP and haplotype of IL-12A +6400/+6624/+7003. Furthermore, no statistically significant association of HCC development with IL-12A exon 7 +6400, +6624, 3' UTR +7003 SNP and haplotype of IL-12A +6400/+6624/+7003 was observed. CONCLUSIONS: These results suggest that SNPs and haplotype of IL-12A are not associated with HBV persistence and development of HCC. Further studies are needed to identify the host genetic factors in immune defense including cytokine gene polymorphisms of both IL-12A and IL-12B.

Kang JK, Cheong JY, Cho SW, Cho JH, Park JS, Kim YB, Kim DJ, Hwang SG, Yang JM, Park YN. · Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea. · Korean J Hepatol. · Pubmed #18159150 links to  free full text

Abstract: BACKGROUND AND AIMS: FibroScan is a new medical device that noninvasively measures liver stiffness. The aim of this study was to assess the accuracy of the liver stiffness measurement by FibroScan for making the diagnosis of liver fibrosis in patients with chronic viral hepatitis. METHODS: We studied 103 patients with chronic viral hepatitis B or C and they underwent FibroScan and liver biopsy between October 2005 and August 2006. Liver fibrosis was staged on a 0-4 scale according to the Korean Society of Pathologists Scoring System. The diagnostic accuracy was assessed by analysis of the receiver operator characteristics (ROC). RESULTS: The liver stiffness was 3.5-57.1 kPa (mean: 11.8, SD: 8.9). The mean value of liver stiffness in each fibrosis stage group (F1, F2, F3 and F4) was 5.8+/-1.8 kPa, 11.3+/-6.8 kPa, 11.8+/-6.0 kPa and 23.4+/-16.5 kPa, respectively. Liver stiffness measured by FibroScan showed reliable correlation with the liver fibrosis stage as confirmed by liver biopsy (r=0.56, p<0.001). The AUROC (95% CI) of > or = F2, > or = F3 and F4 was 0.93 (0.86-0.99), 0.72 (0.62-0.82) and 0.80 (0.67-0.92), respectively. The sensitivity and specificity of 7.5 kPa, which was the cutoff value for > or = F2, was 84% and 90%, respectively. CONCLUSIONS: FibroScan is a reliable method for the diagnosis of significant fibrosis (> or =F2) and cirrhosis in patients with chronic liver disease. The liver stiffness measurement by FibroScan showed good diagnostic performance for significant fibrosis.

Kim BK, Kim SA, Park YN, Cheong JY, Kim HS, Park JY, Cho SW, Han KH, Chon CY, Moon YM, Ahn SH. · Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. · Liver Int. · Pubmed #17696936 No free full text.

Abstract: OBJECTIVES: Few noninvasive models of chronic hepatitis B (CHB) to predict liver cirrhosis have been studied. The aim of the current study is to investigate the diagnostic accuracy of two simple novel models of spleen-platelet ratio index (SPRI) and age-spleen-platelet ratio index (ASPRI) in patients with CHB. PATIENTS AND METHODS: A total of 346 consecutive treatment-naïve patients with CHB were retrospectively studied. The aspartate to alanine aminotransferase ratio (AAR), age-platelet index (API), aspartate aminotransferase to platelet ratio index (APRI), SPRI, and ASPRI were compared with liver histology. RESULTS: AAR, APRI, SPRI, API, and ASPRI correlated significantly to fibrosis stage (all P<0.001). The diagnostic accuracy of ASPRI was the highest among five tests for prediction of cirrhosis (area under receiver operating characteristic curve, AUROC=0.893). Using a cutoff score of ASPRI>12, the presence of cirrhosis could be correctly identified with a high accuracy (96.3% positive predictive value) in 35 (10.1%) of 346 patients. Similarly, using a cutoff of <5, the presence of cirrhosis could be totally excluded with 100% of negative predictive value in 120 (34.7%) of 346 patients. CONCLUSION: ASPRI was accurate in predicting cirrhosis and screening with ASPRI has the potential to reduce the number of liver biopsies in CHB patients.

Cheong JY, Cho SW, Choi JY, Lee JA, Kim MH, Lee JE, Hahm KB, Kim JH. · Department of Gastroenterology, Genomic Research Center for Gastroenterology, Ajou University School of Medicine, San-5 Wonchon-dong, Youngtong-gu, Suwon, Korea. · J Korean Med Sci. · Pubmed #17596666 links to  free full text

Abstract: Recovery from hepatitis B virus (HBV) infection depends on the cellular immune responses. Chemokines and their receptors play significant roles in immune defense. This study was undertaken to investigate the association between HBV infection and single nucleotide polymorphisms (SNPs) of genes for the chemokines and their receptors. Between March 2002 and February 2004, a total of 957 single ethnic Korean patients were enrolled into two different groups; "HBV clearance group" (n=350), who have recovered from HBV infection, and "HBV persistence group" (n=607), who were repeatedly HBsAg-positive. The HBV persistence group was subdivided into "inactive carrier" and "HBV progression group (chronic hepatitis and cirrhosis)". We assessed polymorphisms in regulated and normal T-cell expressed and secreted (RANTES) at position -403, monocyte chemoattractant protein-1 (MCP-1) at position -2518, CCR2 V64I, CCR5 -2459, CXCR1 S276T and CXCR4 I138I using single primer extension assay. Genotype distributions of the "HBV clearance versus persistence group" and "inactive carrier versus HBV progression group" were compared. On the basis of unconditional logistic regression analysis with adjustment for age and sex, no statistically significant association with susceptibility to persistent HBV infection was observed with RANTES -403, MCP-1 -2518, CCR2 V64I, CCR5 -2459, CXCR1 S276T, and CXCR4 I138I polymorphisms. In addition, no association of analyzed SNPs with HBV disease progression was found.

Cheong JY, Cho SW, Chung SG, Lee JA, Yeo M, Wang HJ, Lee JE, Hahm KB, Kim JH. · Department of Gastroenterology, Genomic Research Center for Gastroenterology, Ajou University School of Medicine, San-5 Wonchon-Dong, Youngtong-ku, Suwon, South Korea. · Biochem Genet. · Pubmed #16944293 No free full text.

Abstract: The natural history of hepatitis B virus (HBV) infection is probably related to host immune factors. Interferon-gamma (IFN-gamma) plays significant roles in immune defense. This study was undertaken to investigate the association between HBV infection and single nucleotide polymorphisms (SNPs) of IFN-gamma, IFN-gamma receptor (IFNGR)-1 and 2, and interferon regulatory factor (IRF)-1 genes. Between March 2002 and December 2002, 614 Korean patients were enrolled in two different groups: an HBV clearance group (n = 201), who were hepatitis B surface antigen (HBsAg) negative with antibodies to HBsAg and hepatitis B core antigen, and an HBV persistence group (n = 413), who were repeatedly HBsAg positive. We assessed polymorphisms in the IFN-gamma gene at position +874, in the IFNGR-1 gene at positions -56 and +95, in the IFNGR-2 gene at the second position of codon 64 (Gln64Arg), and in the IRF-1 gene promoter (-410, -388), and the genotype distributions of the HBV clearance and persistence groups were compared. On the basis of unconditional logistic regression analysis with adjustment for age and sex, no statistically significant association with susceptibility to persistent HBV infection was observed with the IFN-gamma, IFNGR-1 and 2, and IRF-1 gene polymorphisms under the codominant, dominant, and recessive models.

Cheong JY, Cho SW, Hwang IL, Yoon SK, Lee JH, Park CS, Lee JE, Hahm KB, Kim JH. · Department of Gastroenterology, Genomic Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, South Korea. · J Gastroenterol Hepatol. · Pubmed #16824070 No free full text.

Abstract: BACKGROUND: The reasons for the viral persistence of hepatitis B virus infection (HBV) are unknown, but are probably related to host immune factors. Cytokines play a significant role in immune defense. The present study was undertaken to investigate the association between HBV infection and polymorphisms of tumor necrosis factor (TNF)-alpha and interleukin(IL)-10 gene promoter. METHODS: A total of 412 Korean patients with HBV infection (72 inactive carriers, 261 with chronic hepatitis, 79 with liver cirrhosis) and 204 healthy individuals who recovered from HBV infection, were studied. The polymorphisms in IL-10 gene promoter (-1082, -819, -592), and TNF-alpha gene promoter (-308, -238) were assessed by single base primer extension assay. RESULTS: The frequency of C/C genotype at position -592 of IL-10 gene promoter was higher in the HBV clearance group than that in the persistence group in univariate analysis (12.7% vs 7.5%, P = 0.036). The IL-10 gene promoter -592 C/C genotype was related to clearance of HBV infection in logistic regression analysis after adjusting for age and sex (P = 0.003). Genotype frequencies of TNF-alpha gene promoter at position -308 and -238 were not different between the clearance and the persistence group in univariate analysis, but in multivariate analysis after adjusting for age and sex, -308G/-238G homozygotes were associated with HBV persistence (P = 0.005). Genotype distributions of both gene promoters in inactive carriers were similar to those in patients with chronic progressive liver disease. CONCLUSIONS: The carriers of the -592A allele in the IL-10 promoter and -308G/-238G haplotype homozygotes in the TNF-alpha promoter region have higher risk of persistent HBV infection.

Sim SJ, Cheong JY, Cho SW, Kim JS, Lim TY, Shin do H, Lim SG, Kim YB, Lee KM, Yoo BM, Lee KJ, Hahm KB, Kim JH. · Department of Gastroenterology, Ajou University College of Medicine, Suwon, Korea. · Korean J Gastroenterol. · Pubmed #15908767 links to  free full text

Abstract: BACKGROUND/AIMS: An ideal noninvasive diagnostic test for hepatic fibrosis should be simple, inexpensive, and accurate. We aimed to find the simple marker for predicting hepatic fibrosis and to compare the accuracy of AST, platelet, AST/ALT ratio and AST to platelet ratio index (APRI) in chronic hepatitis B patients without clinical evidence of cirrhosis. METHODS: A total of one hundred and twenty-six chronic hepatitis B patients who underwent liver biopsy at the Ajou University Hospital from August 1998 to December 2003 were enrolled. Hepatic fibrosis was assessed using the Ludwig classification. Significant fibrosis was defined as fibrosis score of 3 or more. The AST/ALT ratio and APRI were calculated and correlations with hepatic fibrosis were analyzed. RESULTS: APRI showed a significant correlation (r=0.501, p=0.000) with hepatic fibrosis, and was superior to AST, AST/ALT ratio and platelet in predicting fibrosis. Patients with significant fibrosis (fibrosis stage 3, 4) can be identified to have APRI = 1 with sensitivity 71.2% and specificity 70.3%. The sensitivity and specificity of an APRI = 1.5 for cirrhosis (stage 4) were 83.3% and 75.0%. CONCLUSIONS: Simple index using AST and platelet value can predict the presence of significant fibrosis and cirrhosis in chronic hepatitis B patients without clinical evidence of cirrhosis.

Cheong JY, Cho SW, Lim SK, Shin DH, Yoon SK, Lee JE, Hahm KB, Kim JH. · Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea. · J Korean Med Sci. · Pubmed #15716605 links to  free full text

Abstract: Mannose-binding lectin (MBL) plays an important role in immune defense. This study was undertaken to investigate the association between hepatitis B virus infection and polymorphisms of MBL gene. We assessed the single nucleotide polymorphism at codon 54 in exon 1 of MBL in patients with hepatitis B virus infection and HBsAg negative controls in Korean population. A total of 498 enrolled subjects was classified into four groups. Group 1; Clearance, Group 2; Inactive healthy carrier, Group 3; Chronic hepatitis, Group 4; Liver cirrhosis. MBL gene polymorphisms at codon 54 led to three genotypes (G/G, G/A, A/A). When we divided subjects into clearance group (group 1) and persistence group (group 2-4), G/G genotype and A-allele carrier were observed in 55.6% and 44.4% in clearance group, 64.8% and 35.2% in persistence group (p=0.081), respectively. When hepatitis B virus persistent cases were divided into inactive healthy carrier (group 2) and disease progression group (group 3 and 4), MBL gene polymorphisms at codon 54 were not related to disease progression (p=0.166). MBL gene polymorphism at codon 54 was not associated with the clearance of hepatitis B virus infection nor progression of disease in chronic hepatitis B virus infection.

Kim DH, Lee EH, Hwang JC, Jeung JH, Kim do H, Cheong JY, Cho SW, Kim YB. · Department of Gastroenterology, Ajou University College of Medicine, Suwon, Korea. · Taehan Kan Hakhoe Chi. · Pubmed #12499790 links to  free full text

Abstract: Orlistat(Xenical(R), Roche) is considered a safe and effective drug to treat obesity by reduced absorption of 30% digested fat. To date, no serious adverse effects affecting the liver have been published except a case of subacute hepatic failure leading to liver transplantation in a young women with moderate obesity treated with orlistat. We report a case of acute cholestatic hepatitis in a young woman with moderate obesity treated with orlistat: a 33-year-old female admitted for the evaluation of jaundice. Abdominal ultrasonography, ERCP, routine chemistry, viral markers, and a fine needle biopsy of liver were performed. Microscopic findings of the liver biopsy specimen were compatible with acute cholestatic hepatitis. After steroid therapy, liver function was improved.